TTLL6_MOUSE
ID TTLL6_MOUSE Reviewed; 822 AA.
AC A4Q9E8; A2A6M6; B2RQS4; Q3UL10; Q8BVQ1;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Tubulin polyglutamylase TTLL6 {ECO:0000303|PubMed:17499049};
DE EC=6.3.2.- {ECO:0000269|PubMed:17499049, ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21074048, ECO:0000269|PubMed:26829768, ECO:0000269|PubMed:32747782};
DE AltName: Full=Protein polyglutamylase TTLL6 {ECO:0000305|PubMed:17499049};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 6;
GN Name=Ttll6 {ECO:0000312|EMBL:CAM84326.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:CAM84326.1};
RC TISSUE=Testis {ECO:0000312|EMBL:CAM84326.1};
RX PubMed=17499049; DOI=10.1016/j.molcel.2007.04.012;
RA van Dijk J., Rogowski K., Miro J., Lacroix B., Edde B., Janke C.;
RT "A targeted multienzyme mechanism for selective microtubule
RT polyglutamylation.";
RL Mol. Cell 26:437-448(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC36577.1};
RC TISSUE=Blastocyst {ECO:0000312|EMBL:BAE26641.1}, and
RC Testis {ECO:0000312|EMBL:BAC36577.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain {ECO:0000312|EMBL:AAI32204.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21074048; DOI=10.1016/j.cell.2010.10.014;
RA Rogowski K., van Dijk J., Magiera M.M., Bosc C., Deloulme J.C., Bosson A.,
RA Peris L., Gold N.D., Lacroix B., Grau M.B., Bec N., Larroque C.,
RA Desagher S., Holzer M., Andrieux A., Moutin M.J., Janke C.;
RT "A family of protein-deglutamylating enzymes associated with
RT neurodegeneration.";
RL Cell 143:564-578(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=20530212; DOI=10.1083/jcb.201001024;
RA Lacroix B., van Dijk J., Gold N.D., Guizetti J., Aldrian-Herrada G.,
RA Rogowski K., Gerlich D.W., Janke C.;
RT "Tubulin polyglutamylation stimulates spastin-mediated microtubule
RT severing.";
RL J. Cell Biol. 189:945-954(2010).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22246503; DOI=10.1038/ng.1078;
RA Lee J.E., Silhavy J.L., Zaki M.S., Schroth J., Bielas S.L., Marsh S.E.,
RA Olvera J., Brancati F., Iannicelli M., Ikegami K., Schlossman A.M.,
RA Merriman B., Attie-Bitach T., Logan C.V., Glass I.A., Cluckey A.,
RA Louie C.M., Lee J.H., Raynes H.R., Rapin I., Castroviejo I.P., Setou M.,
RA Barbot C., Boltshauser E., Nelson S.F., Hildebrandt F., Johnson C.A.,
RA Doherty D.A., Valente E.M., Gleeson J.G.;
RT "CEP41 is mutated in Joubert syndrome and is required for tubulin
RT glutamylation at the cilium.";
RL Nat. Genet. 44:193-199(2012).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23897886; DOI=10.1083/jcb.201305041;
RA Bosch Grau M., Gonzalez Curto G., Rocha C., Magiera M.M., Marques Sousa P.,
RA Giordano T., Spassky N., Janke C.;
RT "Tubulin glycylases and glutamylases have distinct functions in
RT stabilization and motility of ependymal cilia.";
RL J. Cell Biol. 202:441-451(2013).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=26829768; DOI=10.1038/ni.3356;
RA Xia P., Ye B., Wang S., Zhu X., Du Y., Xiong Z., Tian Y., Fan Z.;
RT "Glutamylation of the DNA sensor cGAS regulates its binding and synthase
RT activity in antiviral immunity.";
RL Nat. Immunol. 17:369-378(2016).
RN [10] {ECO:0007744|PDB:6VZQ, ECO:0007744|PDB:6VZR, ECO:0007744|PDB:6VZS, ECO:0007744|PDB:6VZT, ECO:0007744|PDB:6VZU, ECO:0007744|PDB:6VZV, ECO:0007744|PDB:6VZW}
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 51-503 OF WILD-TYPE AND MUTANT
RP ALA-189/ARG-180/ILE-362 IN COMPLEXES WITH ATP; MAGNESIUM AND TETRAHEDRAL
RP INTERMEDIATES ANALOGS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, AND MUTAGENESIS OF LYS-125; LYS-174; CYS-179;
RP GLN-180; ARG-182; ARG-219; ARG-241; ASN-264; LYS-283; ASP-346; GLU-359;
RP HIS-362; SER-367 AND LYS-377.
RX PubMed=32747782; DOI=10.1038/s41594-020-0462-0;
RA Mahalingan K.K., Keith Keenan E., Strickland M., Li Y., Liu Y., Ball H.L.,
RA Tanner M.E., Tjandra N., Roll-Mecak A.;
RT "Structural basis for polyglutamate chain initiation and elongation by TTLL
RT family enzymes.";
RL Nat. Struct. Mol. Biol. 27:802-813(2020).
CC -!- FUNCTION: Polyglutamylase which modifies both tubulin and non-tubulin
CC proteins, generating alpha-linked polyglutamate side chains on the
CC gamma-carboxyl group of specific glutamate residues of target proteins
CC (PubMed:17499049, PubMed:21074048, PubMed:20530212, PubMed:26829768,
CC PubMed:32747782). Preferentially mediates ATP-dependent long
CC polyglutamate chain elongation over the initiation step of the
CC polyglutamylation reaction (PubMed:17499049, PubMed:21074048,
CC PubMed:20530212, PubMed:26829768, PubMed:32747782). Preferentially
CC modifies the alpha-tubulin tail over a beta-tail (PubMed:17499049,
CC PubMed:20530212, PubMed:21074048, PubMed:32747782). Promotes tubulin
CC polyglutamylation which stimulates spastin/SPAST-mediated microtubule
CC severing, thereby regulating microtubule functions (PubMed:20530212).
CC Mediates microtubule polyglutamylation in primary cilia axoneme which
CC is important for ciliary structural formation and motility
CC (PubMed:22246503). Mediates microtubule polyglutamylation in motile
CC cilia, necessary for the regulation of ciliary coordinated beating
CC (PubMed:23897886). Polyglutamylates non-tubulin protein
CC nucleotidyltransferase CGAS, leading to CGAS DNA-binding inhibition,
CC thereby preventing antiviral defense response (PubMed:26829768).
CC {ECO:0000269|PubMed:17499049, ECO:0000269|PubMed:20530212,
CC ECO:0000269|PubMed:21074048, ECO:0000269|PubMed:22246503,
CC ECO:0000269|PubMed:23897886, ECO:0000269|PubMed:26829768,
CC ECO:0000269|PubMed:32747782}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-glutamate + L-glutamyl-[protein] = ADP + gamma-L-
CC glutamyl-L-glutamyl-[protein] + H(+) + phosphate;
CC Xref=Rhea:RHEA:60144, Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:15517,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:143622,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:17499049,
CC ECO:0000269|PubMed:32747782};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000305|PubMed:17499049, ECO:0000305|PubMed:32747782};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + ATP +
CC L-glutamate = (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein]
CC + ADP + H(+) + phosphate; Xref=Rhea:RHEA:60148, Rhea:RHEA-COMP:15519,
CC Rhea:RHEA-COMP:15675, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:143623,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:17499049,
CC ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21074048,
CC ECO:0000269|PubMed:26829768, ECO:0000269|PubMed:32747782};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000305|PubMed:17499049, ECO:0000305|PubMed:20530212,
CC ECO:0000305|PubMed:21074048, ECO:0000305|PubMed:26829768,
CC ECO:0000305|PubMed:32747782};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:32747782};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.22 uM for glutamylated tubulin {ECO:0000269|PubMed:32747782};
CC KM=1.92 uM for non-glutamylated tubulin
CC {ECO:0000269|PubMed:32747782};
CC Note=kcat is 0.73 min(-1) with glutamylated tubulin as substrate
CC (PubMed:32747782). kcat is 0.04 min(-1) with non-glutamylated tubulin
CC as substrate (PubMed:32747782). {ECO:0000269|PubMed:32747782};
CC -!- SUBUNIT: Found in a complex with CEP41. {ECO:0000250|UniProtKB:Q8N841}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26829768}.
CC Cytoplasm, cytoskeleton {ECO:0000305|PubMed:20530212}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000269|PubMed:17499049}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:17499049}.
CC Note=CEP41 is required for its transport between the basal body and the
CC cilium axoneme. {ECO:0000250|UniProtKB:Q8N841}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:17499049};
CC IsoId=A4Q9E8-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16141072};
CC IsoId=A4Q9E8-2; Sequence=VSP_052729;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis (PubMed:17499049).
CC Expressed in brain, heart, kidney, liver, lung, muscle and trachea
CC (PubMed:17499049). In the brain, specifically expressed in ependymal
CC cilia (PubMed:23897886). {ECO:0000269|PubMed:17499049,
CC ECO:0000269|PubMed:23897886}.
CC -!- DOMAIN: The flexible c-MTBD (cationic microtubule binding domain)
CC region mediates binding to microtubules. It is positively charged and
CC becomes ordered when bound to microtubules: it interacts with a
CC negatively charged patch on tubulin. The presence of positive charges
CC in the c-MTBD region is essential for proper binding.
CC {ECO:0000250|UniProtKB:Q6ZT98, ECO:0000250|UniProtKB:Q8N841}.
CC -!- DOMAIN: Gln-180 is the main determinant for regioselectivity, which
CC segregates between initiases and elongases in all tubulin--tyrosine
CC ligase family. A glutamine residue at this position is found in
CC elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-
CC chain elongation, whereas an arginine residue is found in initiases
CC TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.
CC {ECO:0000269|PubMed:32747782}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC36577.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAM18274.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AM690749; CAM84326.1; -; mRNA.
DR EMBL; AK077033; BAC36577.1; ALT_FRAME; mRNA.
DR EMBL; AK145771; BAE26641.1; -; mRNA.
DR EMBL; AL603682; CAM18273.1; -; Genomic_DNA.
DR EMBL; AL603682; CAM18274.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC132203; AAI32204.1; -; mRNA.
DR EMBL; BC138058; AAI38059.1; -; mRNA.
DR EMBL; BC145131; AAI45132.1; -; mRNA.
DR CCDS; CCDS25290.2; -. [A4Q9E8-1]
DR RefSeq; NP_766387.2; NM_172799.4. [A4Q9E8-1]
DR RefSeq; XP_017170019.1; XM_017314530.1.
DR RefSeq; XP_017170020.1; XM_017314531.1. [A4Q9E8-2]
DR PDB; 6VZQ; X-ray; 3.08 A; A/B/C/D=51-503.
DR PDB; 6VZR; X-ray; 2.60 A; A/B/C/D=51-503.
DR PDB; 6VZS; X-ray; 2.66 A; A/B/C/D=51-503.
DR PDB; 6VZT; X-ray; 2.18 A; A/B=51-503.
DR PDB; 6VZU; X-ray; 1.98 A; A/B/C/D=51-503.
DR PDB; 6VZV; X-ray; 2.33 A; A/B/C/D=51-503.
DR PDB; 6VZW; X-ray; 2.50 A; A/B/C/D=51-503.
DR PDBsum; 6VZQ; -.
DR PDBsum; 6VZR; -.
DR PDBsum; 6VZS; -.
DR PDBsum; 6VZT; -.
DR PDBsum; 6VZU; -.
DR PDBsum; 6VZV; -.
DR PDBsum; 6VZW; -.
DR AlphaFoldDB; A4Q9E8; -.
DR SMR; A4Q9E8; -.
DR STRING; 10090.ENSMUSP00000127778; -.
DR iPTMnet; A4Q9E8; -.
DR PhosphoSitePlus; A4Q9E8; -.
DR PaxDb; A4Q9E8; -.
DR PRIDE; A4Q9E8; -.
DR ProteomicsDB; 298018; -. [A4Q9E8-1]
DR ProteomicsDB; 298019; -. [A4Q9E8-2]
DR Antibodypedia; 17865; 44 antibodies from 12 providers.
DR DNASU; 237930; -.
DR Ensembl; ENSMUST00000107680; ENSMUSP00000103307; ENSMUSG00000038756. [A4Q9E8-2]
DR Ensembl; ENSMUST00000167258; ENSMUSP00000127778; ENSMUSG00000038756. [A4Q9E8-1]
DR GeneID; 237930; -.
DR KEGG; mmu:237930; -.
DR UCSC; uc011ydd.1; mouse. [A4Q9E8-1]
DR CTD; 284076; -.
DR MGI; MGI:2683461; Ttll6.
DR VEuPathDB; HostDB:ENSMUSG00000038756; -.
DR eggNOG; KOG2158; Eukaryota.
DR GeneTree; ENSGT00940000161434; -.
DR HOGENOM; CLU_010131_7_2_1; -.
DR InParanoid; A4Q9E8; -.
DR OMA; AYPIIKH; -.
DR OrthoDB; 1251554at2759; -.
DR PhylomeDB; A4Q9E8; -.
DR TreeFam; TF313087; -.
DR BRENDA; 6.3.2.B3; 3474.
DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin.
DR BioGRID-ORCS; 237930; 2 hits in 70 CRISPR screens.
DR PRO; PR:A4Q9E8; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; A4Q9E8; protein.
DR Bgee; ENSMUSG00000038756; Expressed in spermatid and 29 other tissues.
DR Genevisible; A4Q9E8; MM.
DR GO; GO:0097731; C:9+0 non-motile cilium; IDA:MGI.
DR GO; GO:0036064; C:ciliary basal body; IDA:MGI.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070739; F:protein-glutamic acid ligase activity; IDA:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0070740; F:tubulin-glutamic acid ligase activity; IDA:UniProtKB.
DR GO; GO:0001578; P:microtubule bundle formation; IGI:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051013; P:microtubule severing; IDA:MGI.
DR GO; GO:0003353; P:positive regulation of cilium movement; IMP:MGI.
DR GO; GO:0018095; P:protein polyglutamylation; IDA:UniProtKB.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; IDA:UniProtKB.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR InterPro; IPR027754; TTLL6.
DR PANTHER; PTHR12241:SF96; PTHR12241:SF96; 1.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell projection; Cilium;
KW Cytoplasm; Cytoskeleton; Ligase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..822
FT /note="Tubulin polyglutamylase TTLL6"
FT /id="PRO_0000326161"
FT DOMAIN 57..400
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..266
FT /note="L-glutamate"
FT /evidence="ECO:0000305|PubMed:32747782,
FT ECO:0007744|PDB:6VZU, ECO:0007744|PDB:6VZW"
FT REGION 371..450
FT /note="c-MTBD region"
FT /evidence="ECO:0000250|UniProtKB:Q8N841"
FT REGION 736..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 791..822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 797..822
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 174
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZT"
FT BINDING 180..181
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZT"
FT BINDING 180
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_part="L-glutamate residue"
FT /ligand_part_id="ChEBI:CHEBI:29973"
FT /ligand_part_note="L-glutamate acceptor residue in protein
FT target"
FT /evidence="ECO:0000305|PubMed:32747782"
FT BINDING 202..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZT"
FT BINDING 215..217
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZT"
FT BINDING 241
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000305|PubMed:32747782,
FT ECO:0007744|PDB:6VZU, ECO:0007744|PDB:6VZW"
FT BINDING 263..264
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZT"
FT BINDING 283
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000305|PubMed:32747782,
FT ECO:0007744|PDB:6VZU, ECO:0007744|PDB:6VZW"
FT BINDING 346
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZU"
FT BINDING 359
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZU"
FT BINDING 359
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZU"
FT BINDING 361
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:32747782,
FT ECO:0007744|PDB:6VZU"
FT BINDING 362
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_part="L-glutamate residue"
FT /ligand_part_id="ChEBI:CHEBI:29973"
FT /ligand_part_note="L-glutamate acceptor residue in protein
FT target"
FT /evidence="ECO:0000305|PubMed:32747782"
FT BINDING 377
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000305|PubMed:32747782,
FT ECO:0007744|PDB:6VZU, ECO:0007744|PDB:6VZW"
FT SITE 180
FT /note="Essential for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000269|PubMed:32747782"
FT SITE 362
FT /note="Important for specifying alpha-elongation versus
FT initiation step of the polyglutamylase activity"
FT /evidence="ECO:0000269|PubMed:32747782"
FT VAR_SEQ 1..104
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_052729"
FT MUTAGEN 125
FT /note="K->A: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 174
FT /note="K->A: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 179
FT /note="C->A: Strong increase in alpha-tubulin initiation
FT step of polyglutamylase activity; when associated with R-
FT 180 and I-362. Strong increase in alpha-tubulin initiation
FT step of polyglutamylase activity; when associated with R-
FT 180, I-182, I-362 and H-367."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 179
FT /note="C->V: Decreased alpha-tubulin alpha-elongation step
FT of polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 180
FT /note="Q->A: Decreased alpha-tubulin alpha-elongation step
FT of polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 180
FT /note="Q->R: Increased alpha-tubulin initiation step of
FT polyglutamylase activity. Increased alpha-tubulin
FT initiation step of polyglutamylase activity; when
FT associated with I-362. Strong increase in alpha-tubulin
FT initiation step of polyglutamylase activity; when
FT associated with A-179 and I-362. Strong increase in alpha-
FT tubulin initiation step of polyglutamylase activity; when
FT associated with A-179, I-182, I-362 and H-367."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 182
FT /note="R->I: Strong increase in alpha-tubulin initiation
FT step of polyglutamylase activity; when associated with A-
FT 179, R-180, I-362 and H-367."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 219
FT /note="R->A: Loss of alpha-tubulin alpha-elongation
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 241
FT /note="R->A: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 264
FT /note="N->A: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 283
FT /note="K->A: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 346
FT /note="D->A: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 359
FT /note="E->Q: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 362
FT /note="H->A: Decreased alpha-tubulin alpha-elongation step
FT of polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 362
FT /note="H->I: Small increase in alpha-tubulin initiation
FT step of polyglutamylase activity. Increased alpha-tubulin
FT initiation step of polyglutamylase activity; when
FT associated with R-180. Strong increase in alpha-tubulin
FT initiation step of polyglutamylase activity; when
FT associated with A-179 and R-180. Strong increase in alpha-
FT tubulin initiation step of polyglutamylase activity; when
FT associated with A-179, R-180, I-362 and H-367."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 367
FT /note="S->H: Strong increase in alpha-tubulin initiation
FT step of polyglutamylase activity; when associated with A-
FT 179, R-180, I-182 and I-262."
FT /evidence="ECO:0000269|PubMed:32747782"
FT MUTAGEN 377
FT /note="K->A: Loss of alpha-tubulin alpha-elongation step of
FT polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:32747782"
FT CONFLICT 195
FT /note="P -> A (in Ref. 2; BAC36577)"
FT /evidence="ECO:0000305"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 70..79
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 101..105
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:6VZU"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 125..138
FT /evidence="ECO:0007829|PDB:6VZU"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:6VZU"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 156..165
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:6VZU"
FT TURN 180..183
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:6VZT"
FT STRAND 216..226
FT /evidence="ECO:0007829|PDB:6VZU"
FT TURN 227..230
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 231..242
FT /evidence="ECO:0007829|PDB:6VZU"
FT TURN 252..256
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 258..261
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 265..268
FT /evidence="ECO:0007829|PDB:6VZU"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 286..295
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 300..329
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 341..350
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 355..363
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 371..387
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 395..411
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 415..439
FT /evidence="ECO:0007829|PDB:6VZU"
FT STRAND 444..449
FT /evidence="ECO:0007829|PDB:6VZU"
FT HELIX 453..459
FT /evidence="ECO:0007829|PDB:6VZU"
SQ SEQUENCE 822 AA; 94507 MW; C262476CB0A937A1 CRC64;
MLQCLTSESE EGAEEREESS TEDLEELKEF VTLAFVRENT QKRLQNAQQH GKKKRKKKRL
VINLSNCRYD SVRRAAQQYG LREAGDNDDW TLYWTDYSVS LERVMEMKSY QKINHFPGMS
EICRKDLLAR NMSRMLKLFP KDFHFFPRTW CLPADWGDLQ TYSRTRKNKT YICKPDSGCQ
GRGIFITRSV KEIKPGEDMI CQLYISKPFI IDGFKFDLRV YVLVTSCDPL RVFVYNEGLA
RFATTSYSHP NLDNLDEICM HLTNYSINKH SSNFVQDAFS GSKRKLSTFN SYMKTHGYDV
EQIWRGIEDV IIKTLISAHP VIKHNYHTCF PSHTLNSACF EILGFDILLD RKLKPWLLEV
NHSPSFSTDS KLDKEVKDSL LYDALVLINL GNCDKKKVLE EERQRGRFLQ QCPNREIRLE
EVKGFQAMRL QKTEEYEKKN CGGFRLIYPG LNLEKYDKFF QDNSSLFQNT VASRARELYA
RQLIQELRQK QEKKVFLKKA RKEETQGESA GEQARDKVVR LQRQRQQPKC KTVATCPPKQ
SLHPVTLVSC TSGLLLNIRG LKKGEISESL EQKDTKEAML IPCKPVSARN YSSVPDLRSA
NPSCFEPEFH VPNAKVKEVK SAFMVNIEST AQPITSVESS RDATAPISTS LESLASMSLS
TSPECSSPES VHMVSYNHKQ QKASFHKPMQ EKKSKPLMFS KSRHLDLNCT SMKNDINRQY
LMSEILQKVQ MKKKRPLFPA PKSQYPTLSK ERCPHSRSSS RKKEMNSPSV FVLQASHSRA
ESLNDLLVVA TQARLDPRPS RSHSGTTTRD SSTQDPKHTA TA
